Field of the Invention
This invention is directed to new organic compounds and is particularly concerned with novel 7-phenylpyrimido[1,2-a][1,4]benzodiazepin-3(5H)-ones (II) and the process therefor. The invention furthermore includes the pharmaceutically acceptable acid addition salts.
The novel compounds II, intermediates, and the process of production thereof can be illustratively represented as follows: ##STR9## wherein R'.sub.0 is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, --COOR in which R is alkyl defined as above, and ##STR10## in which n is a number from 1 to 4, R.sub.6 and R.sub.7 are alkyl defined as above, or together ##STR11## is selected from the group consisting of pyrrolidino, piperidino, morpholino, and 4-methylpiperazino; wherein R.sub.1 is selected from the group consisting of hydrogen, hydroxy, acetoxy, propionoxy, hydrogen succinyloxy, and alkylsuccinyloxy in which alkyl is defined as above; wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, halogen, nitro, cyano, trifluoromethyl, and alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, and alkanoylamino in which the carbon moiety is of 1 to 3 carbon atoms, inclusive, and dialkylamino in which alkyl is defined as above, and Ac is acetyl.
The compounds wherein R.sub.0 is hydroxymethyl are produced from those wherein R.sub.0 ' is --COOR (R being alkyl of 1 to 3 carbon atoms, inclusive) by selective reduction with lithium aluminum hydride.
The preferred product of this invention are those of the formula IIe: ##STR12## wherein R.sub.0 is defined as above; and wherein R.sub.2, R.sub.3, and R.sub.4 are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, and alkylthio in which alkyl is of 1 to 3 carbon atoms, inclusive.
More preferred still are those compounds of formula IIf: ##STR13## wherein R.sub.0 is defined as above and R.sub.2, R.sub.3, and R.sub.4 are selected from the group consisting of hydrogen and chlorine.
Furthermore this invention includes the compound of formula II (which formula includes the subspecies IIa, IIb, IIc, IId, IIe, and IIf) as acid addition salts of pharmacologically acceptable acids. Both, the free base and the pharmacologically acceptable acid addition salts are useful as tranquilizing and sedative agents.
The basic process of this invention comprises: the formation of the pyrimido ring by reaction of an amine of formula I with a reagent selected from the group consisting of HC.tbd.C--COOR, ROOC--C.tbd.C--COOR in which R is alkyl as defined above and ##STR14## in which R' is alkyl as defined above or ##STR15## in which n, R.sub.6, and R.sub.7 are defined as above.